Protect effect of bicyclol on cisplatin-induced nephrotoxicity in mice.
This study investigated the protective effects of bicyclol against cisplatin-induced nephrotoxicity and the possible mechanisms in mice. Bicyclol (250 mg/kg, p.o., 5 days) showed significant protection as evidenced by the decrease of elevated serum creatine and blood urea nitrogen, and improvement of histopathological injury induced by cisplatin. The formation of kidney malondialdehyde with a concomitant reduction of reduced glutathione were also inhibited by bicyclol, while the activities of kidney superoxide dismutase, catalase and glutathione peroxidase were all increased, respectively. Bicyclol also inhibited the increase of kidney and serum nitric oxide induced by cisplatin. In addition, induction of induced nitric oxide synthase and nitrotyrosine were suppressed by bicyclol. Bicyclol suppressed cisplatin-induced extracelluar signal regulated kinases 1/2 and p38 mitogen-activated protein kinase activation in the kidney of mice. Results obtained demonstrate that bicyclol pre-administration can prevent the nephrotoxicity induced by cisplatin.
Yu
Ying-Nan
YN
Department of New Drug Development, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1, Xian Nong Tan Street, 100050 Beijing, People's Republic of China. yuyingnan@imm.ac.cn
Chen
Hui
H
Li
Yan
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D002945:Cisplatin / Q000633:toxicity*; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; C477843:bicyclol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D005978:Glutathione; D002945:Cisplatin